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The role of XBP-1 in osmotic activated-lipid synthesis.Malvicini R; Weber K; Goldman L, Mancovsky S, Saban T; Casali CI*, Fernández M*,*Both are considered last authors. Biología Celular y Molecular, Fac. Farmacia y Bioquímica, UBA. IQUIFIB-CONICET. Escuelas Técnicas ORT. CABA. Argentina.E-mail: fertome@ffyb.uba.ar.It is known that hypertonicity induces an abrupt synthesis of several osmoprotective proteins such as urea transporters, COX2, AQP2, AQP3, among others, and organic osmolytes. It is also known that a massive protein synthesis could cause endoplasmic reticulum (ER) stress. Previously, we showed that hypertonicity activates the expression of ER stress markers in MDCK cells subjected to high NaCl concentrations, XBP-1 and CHOP, among them. The active form of XBP-1 is a transcription factor that activates the expression of lipogenic genes which, in turn, activate membrane biogenesis and ER stress alleviation. As hypertonicity significantly increases lipid synthesis in renal cells, in the present work we evaluated whether XBP-1 is involved in such response. To do that, prior to hypertonicity treatment, MDCK cultures were treated with XBP1siRNA. After 24 h of hypertonic treatment, the synthesis of lipids and the expression of key lipogenic enzymes were assayed. NaCl treatment, significantly increased the synthesis of both phospholipids (PL) and triglycerides (TAG); XBP1 silencing reduced the levels 1,2 DAG and TAG formed. This finding was consistent with the decrease in the levels of Lipin2 and DGAT2 mRNA. Interestingly, PL synthesis was not affected. These results clearly evidence a major role of XBP1 in the regulation of lipid synthesis in renal epithelial cells.